Laboratory of functional organization of the cell nucleus

The laboratory was organized in 2001 to study ribosome biogenesis and particularly the functions of the main nuclear structural domain, the nucleolus in mammalian and human cells. The current laboratory researches aimed at solving the fundamental issues on the roles of nucleolar proteins in making ribosomes and  also on their involvement in other vital processes, such as regulation of cell cycle and proliferation in normal and cancer cells. From a practical standpoint, these studies intend to identify novel – the nucleolar – targets for gene therapy of cancer, to elucidate mechanisms of production of autoantibodies to nucleolar proteins, to elaborate non-invasive approaches for testing new drugs, which affect the processes occurring with the involvement of the nucleolus.

Immunocytochemical localization of key nucleolar proteins such as UBF (the specific nucleolar co-factor of RNA polymerase I; left), fibrillarin (an early rRNA processing factor and the main nucleolar methyltransferase; middle) and B23/NPM1/nucleophosmin (multifunctional protein; right) in HeLa human cancer cells. The blue color shows chromatin, NUO - nucleoli.

The laboratory collaborates with other laboratories in the Institute, as well as with the Faculty of Biology of the Moscow State UniversityFaculty of Bioengineering and Bioinformatics of  the Moscow State UniversityA.N. Belozersky Institute of Physico-Chemical Biology of the Moscow State UniversityN.N. Semenov Chemical Physics Institute of the RASN.K. Koltsov Institute of Developmental Biology fof the RASInstitute of Molecular Genetics of the RAS, Institute of Cytology of the RASJagiellonian University in Krakow (Poland),  Institute of Cell and Molecular Science of Barts and The London School of Medicine and Dentistry (UK), University Claude Bernard in Lyon (France) and others.

• Studying of specific properties and functions of the nucleolar protein involved in ribosome biogenesis and regulation of cell proliferation in normal and cancer mammalian cells.

• Analysis of the nucleolar reaction on inhibition of transcription and translation and on oxidative stress in human cells. Studying the specificity of the nucleolar protein response to various cell injuries by modern microscopy.

• Elaboration of laboratory experimental models for elucidation of the mechanisms of systemic autoimmune diseases in man and of involvement in this process the nucleolar proteins as autoantigens. Analysis of the capability of anti- nucleolar autoimmune antibodies to penetrate into living cells in various organs and of their putative cytotoxic effects.

• Analysis of roles of nucleolus-derived bodies, which are formed in mammalian fully-grown oocytes and early embryos instead of normal nucleoli, in making ribosomes.

1. Were identified oligomeric forms of the multifunctional nucleolar protein B23/NPM1/nucleophosmin specific for different types of tumor cells. Were raised specific antibodies to the major B23 isoforms (B23.1 and B23.2) (in co-laboration with Prof. O. M. Volpina).

2. Was proven that the nucleolar evolutionarily conserved rRNA processing factor SURF6 is involved in regulation of cell proliferation and serves as a new proliferative marker in PHA-activated lymphocytes in vitro. Was shown that SURF6 is not detected in normal lymphocytes but becomes expressed in patients with lymphoproliferative diseases. These data allow us to consider SURF6 as a new prognostic marker for lymphatic leukemia.

3. By regular administrations of sub-lethal doses of HgCl2 to SJL inbreed mice was elaborated a laboratory model of human systemic autoimmune diseases accompanied by production of anti-nucleolar antibodies. The model was successfully used for the screening of new immunosuppressive agents (in co-laboration with Dr. M.S. Kraschichikova and Prof. V.I. Deigin) .

4. Were described the major parameters for assessment of the dynamics of nucleolar proteins in living cells by FRAP (fluorescence recovery after photobleaching).

5. Was shown that the nucleolus-like of pre-ovulatory mammalian oocytes (for example, the mouse GV oocytes) contain all of the key proteins and rRNAs of typical nucleolus and therefore are capable to produce ribosomes.

6. Was proved that, despite the striking morphological similarity, "nucleoli" in mouse pre-ovulatory oocytes and zygotic embryos differ in biochemical composition and most likely play different roles in mammalian development.

7. Were developed additional criteria of the GV oocyte competence for meiotic maturation based on the capability of nuclei to migrate in the oocyte interior.

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Olga Zatsepina